Blood clotting is a complex process involving multiple initiators and cascades of activators which ultimately lead to the formation of fibrin and eventually to insoluble fibrin clots. The blood clotting process is an indicator of serious pathological conditions including thrombosis, pulmonary embolism, heart attack, stroke, and coronary artery disease which is the primary cause of mortality in the United States.
Conventionally, blood clotting process is assessed by measuring the time taken for a sample of blood to clot naturally or after a specific chemical coagulation initiator is introduced. The most commonly used tests for measuring the blood clotting time are the activated partial thromboplastin time (aPTT) test and prothrombin time (PT) test. The former is initiated by kaolin, PL (an emulsion of negatively charged phospholipids), and calcium; and the latter is initiated by thromboplastin and calcium. The conventional methods for determining the time of clot formations are typically based on mechanical, acoustical or electrical technologies. These methods are relatively slow and the instruments involved can be relatively bulky.
Optical measurements have been used in determining blood clotting time in vitro. U.S. Pat. No. 4,777,141 (to Calzi et al) discloses an instrument for measuring coagulation parameters, in which plasma and a reagent is mixed and a light scatter measurement is made on the mixture. The light scatter measurement is based on the transition of an initial homogenous liquid phase to a heterogeneous light-solid phase in which the threads of insoluble fibrin are formed.
U.S. Pat. No. 5,039,617 (McDonald et al) discloses a capillary flow device and the method for measuring activated partial thromoplastin time. This method performs an APTT analysis on a whole blood sample to which no anticoagulant has been added, by applying the sample to a capillary track, and by detecting the cessation of blood flow as determined by a light scatter measurement on blood cells passing through a specific location of the track.
On the other hand, U.S. Pat. No. 6,958,816 (to Dogariu et al) discloses methods and systems that use dynamic light scattering, for investigating local rheological responses of complex fluids over a frequency range larger than that provided by standard instrumentation.
Currently, no instrument is available for monitoring blood coagulation status in vivo in real time. It is known that patients who have undergone major surgery are at great risk of thrombosis up to 72 hrs after surgery. Under these conditions any significant increase in blood viscosity may most probably indicate the onset of thrombosis.
Therefore, there is a strong need for instrumentations and methodologies that enable early detection of clotting activation in real time, so that early therapeutic intervention can be started timely to avert thrombosis and death. Furthermore, there is further a strong need in the ability of monitoring the effectiveness of procoagulant or anticoagulant therapies in real time, which would allow the physicians to understand and control the therapeutic treatment. Moreover, it is also desirable to effectively monitor coagulation activities in vitro, and provide improved detection method for determining clotting time.